A randomized, controlled trial of postoperative adjuvant interferon therapy after resection of hepatocellular carcinoma

Abstract

Objective: We conducted a randomized controlled trial of adjuvant interferon therapy in patients with predominantly hepatitis B-related hepatocellular carcinoma (HCC) to investigate whether the prognosis after hepatic resection could be improved.

Summary background data: Recurrence is common after hepatic resection for HCC. Interferon possesses antiviral, immunomodulatory, antiproliferative, and antiangiogenic effects and may be an effective form of adjuvant therapy.

Patients and methods: Since February 1999, patients with no residual disease after hepatic resection for HCC were randomly assigned with stratification by pTNM stage to receive no treatment (control group), interferon alpha-2b 10 MIU/m (IFN-I group) or 30 MIU/m (IFN-II group) thrice weekly for 16 weeks. Enrollment to the IFN-II group was terminated from January 2000 because adverse effects resulted in treatment discontinuation in the first 6 patients. By June 2002, 40 patients each had been enrolled into the control group and IFN-I group. The baseline clinical, laboratory, and tumor characteristics of both groups were comparable.

Results: The 1- and 5-year survival rates were 85% and 61%, respectively, for the control group and 97% and 79%, respectively, for the IFN-I group (P = 0.137). After adjusting for the confounding prognostic factors in a Cox model, the relative risk of death for interferon treatment was 0.42 (95% CI, 0.17-1.05; P = 0.063). Exploratory subset analysis showed that adjuvant interferon had no survival benefit for pTNM stage I/II tumor (5-year survival 90% in both groups; P = 0.917) but prevented early recurrence and improved the 5-year survival of patients with stage III/IVA tumor from 24% to 68% (P = 0.038).

Conclusion: In a group of patients with predominantly hepatitis B-related HCC, adjuvant interferon therapy showed a trend for survival benefit, primarily in those with pTNM stage III/IVA tumors. Further larger randomized trials stratified for stage are needed.

Figures

FIGURE 1. Flow diagram of the progress of the trial.

FIGURE 2. Probability of disease-free survival in patients treated with adjuvant interferon therapy (dotted line) and in patients of the control group (solid line) (log-rank test, P = 0.311).

FIGURE 3. Probability of survival in patients treated with adjuvant interferon therapy (dotted line) and in patients of the control group (solid line) (log-rank test, P = 0.137).

FIGURE 4. Probability of survival in patients with pTNM stage III/IVA tumors treated with adjuvant interferon therapy (dotted line) and in patients of the control group (solid line) (log-rank test, P = 0.038).